CARD15: a pleiotropic autoimmune gene that confers susceptibility to psoriatic arthritis.

A recent genomewide scan in psoriatic arthritis (PsA) revealed a susceptibility locus at 16q. This region overlaps CARD15, a susceptibility gene in Crohn disease. The possibility of a common susceptibility gene between PsA and Crohn disease is further supported by epidemiological studies that note an increased incidence of psoriasis in subjects with Crohn. We screened 187 patients with PsA and 136 healthy controls, all from Newfoundland, for the three common, independent sequence variants of CARD15 (R702W, leu1007fsinsC, and G908R), which were detected by polymerase chain reaction by use of allele-specific primers and visualized through gel electrophoresis. In total, 53/187 (28.3%) probands with PsA had at least one variant of the CARD15 gene, compared with 16/136 (11.8%) controls (odds ratio 2.97; 95% confidence interval 1.61-5.47; P=.0005). Allele frequencies of R702W, leu1007fsinsC, and G908R were 10.43%, 3.21%, and 1.61%, respectively, in patients with PsA, compared with 3.31%, 2.57%, and 0.37%, respectively, in the control patients. CARD15 conferred susceptibility to PsA independent of HLA-Cw*0602. Thus, CARD15 represents a pleiotropic autoimmune gene and is the first non-MHC gene to be associated with PsA.

Mortality in systemic sclerosis (scleroderma).

Two hundred and thirty-seven patients with systemic sclerosis were followed prospectively in a scleroderma clinic. The overall 3, 6, and 9-year survival rates were 86, 76 and 61 per cent respectively. Renal, cardiac and pulmonary disease, and older age at enrollment were adverse prognostic factors associated with reduced survival. There were no significant differences in survival between males and females or in patients with restricted compared to those with diffuse skin thickening. Death from systemic sclerosis was most frequently due to pulmonary hypertension, with fewer than expected deaths from renal or cardiac causes. Twenty-eight per cent of deaths were due to causes unrelated to systemic sclerosis, most commonly cancer and ischaemic heart disease, and in older patients.

Protective HLA-DR phenotypes in rheumatoid arthritis.

In a study of HLA-DR phenotypes in patients with rheumatoid arthritis (RA) and controls from the Saskatoon area and in Newfoundland, we found that certain phenotypes occurred more frequently in the patients than in healthy controls in both populations ("increased risk phenotypes"). The reverse was also true: certain phenotypes were reduced or excluded from patients with RA compared with controls. Three increased risk phenotypes with twice the expected frequencies or more were HLA-DR1,DR4; DR4 and DR4,DR5. Four "protective" phenotypes with half or less the expected frequencies were HLA-DR1, DR5; DR2; DR2,DR3 and DR3,DR7. We speculate that at least for the DR3,DR7 phenotype, the protective effect may be due to a hybrid DQw2 molecule.

The clinical significance of coagulation abnormalities in systemic sclerosis (scleroderma).

A coagulation screen and measurement of circulating factor VIII related antigen (VIII-RAg), factor VIII coagulant activity (VIII-C) and beta-thromboglobulin (beta TG) levels were carried out in 25 patients with systemic sclerosis and 25 age and sex matched controls. Both VIII-RAg and beta TG levels were significantly higher in the systemic sclerosis patients than controls. Fibrin degradation products were increased in 11 (44%) of the patients. There was a significant correlation between the VIII RAg/VIII-C ratio and severity of the vascular abnormalities noted on nailfold capillary microscopy. Those with VIII-RAg levels in excess of 200% of controls (10 of 25) had more severe disease with greater mean number of organ systems involved.